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Molecular Mechanisms of thermosensation and nociception

 We mainly investigate molecular mechanisms of thermosensation and nociception by focusing on so called ‘thermosensitive TRP channels’. Among the huge TRP ion channel superfamily proteins, there are eleven thermosensitive TRP channels in mammals (TRPV1, TRPV2, TRPV3, TRPV4, TRPM2, TRPM3, TRPM4, TRPM5, TRPM8, TRPA1, TRPC5) whose temperature thresholds for activation range from cold to hot.  Because temperatures below 15oC and over 43oC are known to cause pain sensation in our body, some of the thermosensitive TRP channels whose temperature thresholds are in the range can be viewed as nociceptive receptors.  Indeed, TRPV1 and TRPA1 are activated by various nociceptive stimuli including chemical compounds causing pain sensation.  Some of the thermosensitive TRP channels are expressed in the organs or cells which are normally not exposed to the dynamic temperature changes.  We found that they contribute to the various cell functions under the body temperature conditions in the normal to febrile range. Molecular and cell biological, biochemical, developmental and electrophysiological (patch-clamp and calcium-imaging methods) techniques are utilized to clarify the molecular mechanisms of thermosensation and nociception.  In order to understand functions of thermosensitive TRP channels in vivo, we are also doing behavioral analyses using mice lacking the thermosensitive TRP channels. In the evolutionary process, organisms are thought to have adapted the changes in ambient temperature by altering the expression and functions of the thermosensitive TRP channels. Accordingly, we are characterizing the thermosensitive TRP channels from various species, which would help us to understand the mechanisms of thermosensation.  In addition, we are investigating using Drosophila.

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Eleven thermosensitive TRP channels

Typical paper information

* TRPV4 heats ups ANO1-dependent exocrine gland fluid secretion. FASEB J. (in press)
*Characterization of TRPA channels in the starfish Patiria pectinifera: involvement of thermally activated TRPA1 in thermotaxis in marine planktonic larvae. Sci. Rep. 7: 2173, 2017.
*Lysophosphatidic acid-induced itch is mediated by signaling of LPA5 receptor, phospholipase D and TRPA1/TRPV1. J. Physiol. 595: 2681-2698, 2017.
* Requirement of Extracellular Ca2+ Binding to Specific Amino Acids for Heat-evoked Activation of TRPA1. J. Physiol. 595: 2451-2463, 2017.
*Takayama Y, Furue H, Tominaga M. 4-isopropylcyclohexanol has potential analgesic effects through the inhibition of anoctamin 1, TRPV1 and TRPA1 channel activities. Sci. Rep. 7: 43132, 2017.
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